I'll start with a new favourite:
Postler
It's simple, cute and (on my system at least) uses less than 8MB of RAM
Obviously it doesn't do very much but then that's rather the point; do-everything clients like Thunderbird and Evolution are bloody complicated to set up and then use masses of resources.
It's not release-ready yet but is definitely one to watch. I predict Postler becoming the default on a lot of lighter distros.